This project is to establish a new humanized mouse model for the study of immune responses to HIV infection and vaccination. The model utilizes severely immunocompromised mice reconstituted with human thymic and liver tissue, which establishes human lymphocytic and monocytic populations susceptible to HIV infection. We have immunized the animals against HIV-1 CD4+ T cell epitopes and are now studying immune responses. An immediate goal is to determine whether the presence of HIV-1-specific CD4+ memory cells mount effective immune responses to control HIV infection, or act as targets for infection and cause an increase in susceptibility.